The goal of the proposed research remains characterization of the innervation to the anterior segment of the eye by histochemical and biochemical means, with continued emphasis in the following areas. We shall describe the distribution of intraocular nerves fibers containing biologically active peptides, integrating comparative interspecies evaluation to findings in human tissues. To define the origin of specific nerve types in the anterior segment, studies will include histochemical analysis of peripheral ganglia serving the eye, examination of these ganglia after injection into the anterior chamber of markers for retrograde axoplasmic transport, and direct study of ocular tissues after selective denervations. We shall study intensively co-localization patterns of neuropeptides and neurotransmitters in peripheral ocular nerves using neuroanatomical approaches that combine several techniques. We shall undertake biochemical isolation and characterization of selected neuropeptides as an important complement to our histochemical work. In addition, we shall extend our efforts to in vitro autoradiography with the goal of defining the regional characteristics of ocular receptors to biologically active peptides. Through coordination of anatomical, histochemical, biochemical and autoradiographic methods, we seek improved understanding of the ocular innervation and clarification of neural mechanisms governing ocular physiology. These studies are directly related to the pathophysiology of important ocular disorders, and accordingly we shall emphasize relevant ocular tissues. Furthermore, because of the importance of neural mechanisms in ocular pharmacology, these studies likely will continue to suggest novel clinical therapies.